Pathogenesis of PACG: In the Genes?

Author: Jeannette Y. Wick, RPh, MBA, FASCP

An international consortium of researchers has discovered 3 genetic anomalies associated with primary angle closure glaucoma (PACG), which may help lead to the development of new treatments.
Primary angle closure glaucoma (PACG) has joined the long list of diseases for which genetic contributors have been identified. In a study published in the October 2012 edition of Nature Genetics, researchers identified 3 new genetic mutations associated with PACG, a leading cause of blindness affecting 15 million people worldwide, 80% of whom live in Asia or are of Asian descent. PACG blinds proportionately more people than primary open-angle glaucoma globally, and epidemiological studies have indicated one’s risk of developing it is strongly influenced by heredity.

In the study, an international consortium of researchers conducted a genome-wide association study in 2 stages. In the first stage, discovery, they looked at 1854 subjects with PACG cases and 9608 controls in Singapore, Hong Kong, India, Malaysia, and Vietnam. Stage 2, validation, added another 1917 PACG cases and 8943 controls collected from China, Singapore, India, Saudi Arabia, and the United Kingdom.

The team found that a significantly increased risk of developing PACG was associated with anomalies at 3 points in the human genome, known as single-nucleotide polymorphisms (SNPs). The discovery of these genetic markers may help lead to the development of new treatments for PACG by indicating genes that encode for possible targets for new drugs or biologics. At some point, researchers may be able to genotype patients and determine which treatments are more likely to lead to symptom response for them.

The prevalence of PACG is particularly high among older Asians, and the number of people worldwide with the condition will increase dramatically in the coming decades. All health care providers need to heighten their awareness of this condition and its close association with Asian heritage.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.